Tuning Acid-Base Chemistry at an Electrified Gold/Water Interface.

Acid-base reactions are ubiquitous in solution chemistry, as well as in electrochemistry. However, macroscopic concepts derived in solutions, such as pKa and pH, differ significantly at electrified metal-aqueous interfaces due to specific solvation and applied voltage. Here, we measure the pKa values of an amino acid, glycine, at a gold/water interface under a varying applied voltage by means of spectroscopic titration. With the help of simulations, we propose a general model to understand potential-dependent shifts in pKa values in terms of local hydrophobicity and electric fields. These parameters can be tuned by adjusting the metal surface and applied voltage, respectively, offering promising, but still unexplored, paths to regulate reactivity. Our results change the focus with respect to common interpretations based on, for example, apparent local pH effects and open interesting perspectives for electrochemical reaction steering.

3D full-field fringe projection measurement based on imaging view transformation.

To address the loss of measurement information caused by limitation of the field of view in fringe projection profilometry, a 3D full-field measurement based on imaging view transformation with a mirror auxiliary is proposed in this work. In this system, the principle of ideal specular reflection is applied to create a symmetrical structure between the real and virtual images for subsequent imaging view transformation. The phase of images is obtained by a multifrequency and multiple phase-shift sinusoidal fringe projection algorithm, and the real and virtual point clouds of measured objects are obtained by system calibration. The specular reflection matrix is obtained by calculating the relationship between virtual and real corner points. As a result, incomplete real point clouds can be compensated with virtual point clouds for the 3D full-field measurement by imaging view transformation. Compared to the standard ladder, the mean absolute error and the maximum relative error are 0.0706 mm and 0.9834%, respectively.

A splicing variation in NPRL2 causing familial focal epilepsy with variable foci: additional cases and literature review.

NPRL2 (nitrogen permease regulator like 2) is a component of the GATOR1(GAP activity towards rags complex 1) proteins, which is an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. GATOR1 complex variations were reported to correlate with familial focal epilepsy with variable foci (FFEVF). However, FFEVF caused by NPRL2 variants has not been widely explored. Here, we describe a variant, 339+2T>C, in NPRL2 identified by trio whole-exome sequencing (WES) in a family. This splicing variant that occurred at the 5' end of exon 3 was confirmed by minigene assays, which affected alternative splicing and led to exon 3 skipping in NPRL2. Our cases presented multiple seizure types (febrile seizures, infantile spasms, focal seizures, or focal to generalized tonic-clonic seizures). Electroencephalogram (EEG) showed frequent discharges in the left frontal and central regions. A favorable prognosis was achieved in response to vitamin B6 and topiramate when the patient was seven months old. Our study expands the phenotype and genotype spectrum of FFEVF and provides solid diagnostic evidence for FFEVF.

Rotating Day and Night Disturb Growth Hormone Secretion Profiles, Body Energy Metabolism, and Insulin Levels in Mice.

BACKGROUND: Insulin and growth hormone (GH) - 2 vital metabolic regulatory hormones - regulate glucose, lipid, and energy metabolism. These 2 hormones determine substrate and energy metabolism under different living conditions. Shift of day and night affects the clock system and metabolism probably through altered insulin and GH secretion. METHODS: Five-week-old male mice were randomly assigned to a rotating light (RL) group (3-day normal light/dark cycle followed by 4-day reversed light/dark cycle per week) and normal light (NL) group. Body weight and food intake were recorded every week. Series of blood samples were collected for pulsatile GH analysis, glucose tolerance test, and insulin tolerance test at 9, 10, and 11 weeks from the start of intervention, respectively. Indirect calorimetric measurement was performed, and body composition was tested at 12 weeks. Expressions of energy and substrate metabolism-related genes were evaluated in pituitary and liver tissues at the end of 12-week intervention. RESULTS: The RL group had an increased number of GH pulsatile bursts and reduced GH mass/burst. RL also disturbed the GH secretion regularity and mode. It suppressed insulin secretion, which led to a disturbed insulin/GH balance. It was accompanied by the reduced metabolic flexibility and modified gene expression involved in energy balance and substrate metabolism. Indirect calorimeter recording revealed that RL decreased the respiratory exchange ratio (RER) and oxygen consumption at the dark phase, which resulted in an increase in fat mass and free fatty acid levels in circulation. CONCLUSION: RL disturbed pulsatile GH secretion and decreased insulin secretion in male mice with significant impairment in energy, substrate metabolism, and body composition.

Effects of food on the pharmacokinetics of ensartinib in healthy Chinese subjects.

Ensartinib is a promising, aminopyridazine-based small molecule that potently inhibits anaplastic lymphoma kinase. This random, two-period, crossover study evaluated the effects of food on the pharmacokinetics of ensartinib after a single dose (225 mg) in healthy Chinese subjects. The pharmacokinetic parameters of ensartinib were calculated using non-compartmental analysis. Twenty-four healthy Chinese subjects age 20-44 years were included in this study. The area under the concentration-time curve of ensartinib was ~25% lower after the intake of a high-fat, high-calorie meal before dosing, whereas the maximum plasma concentration was decreased by ~37%, illustrating the statistically significant effect of food on ensartinib pharmacokinetics. In addition, food intake prolonged the absorption phase of ensartinib (median time to maximum plasma concentration, from 4.5 to 6 hours). Population pharmacokinetic (PopPK) analysis was conducted using NONMEM, and the influences of food, age, sex, body weight and body mass index were studied via covariate analysis. In this analysis, ensartinib plasma concentrations were best described by a one-compartment model with Weibull absorption. The final model included food and age as covariates on apparent distribution and apparent clearance. Based on the final PopPK model, food was identified as a significant covariate for apparent clearance, apparent volume of distribution and absorption rate constant, consistent with the results of non-compartmental pharmacokinetic analysis.

Maintenance of low driving pressure in patients with early acute respiratory distress syndrome significantly affects outcomes.

BACKGROUND: Driving pressure (∆P) is an important factor that predicts mortality in acute respiratory distress syndrome (ARDS). We test the hypothesis that serial changes in daily ΔP rather than Day 1 ΔP would better predict outcomes of patients with ARDS. METHODS: This retrospective cohort study enrolled patients admitted to five intensive care units (ICUs) at a medical center in Taiwan between March 2009 and January 2018 who met the criteria for ARDS and received the lung-protective ventilation strategy. ∆P was recorded daily for 3 consecutive days after the diagnosis of ARDS, and its correlation with 60-day survival was analyzed. RESULTS: A total of 224 patients were enrolled in the final analysis. The overall ICU and 60-day survival rates were 52.7% and 47.3%, respectively. ∆P on Days 1, 2, and 3 was significantly lower in the survival group than in the nonsurvival group (13.8 ± 3.4 vs. 14.8 ± 3.7, p = 0.0322, 14 ± 3.2 vs. 15 ± 3.5, p = 0.0194, 13.6 ± 3.2 vs. 15.1 ± 3.4, p = 0.0014, respectively). The patients were divided into four groups according to the daily changes in ∆P, namely, the low ∆P group (Day 1 ∆P < 14 cmH2O and Day 3 ∆P < 14 cmH2O), decrement group (Day 1 ∆P ≥ 14 cmH2O and Day 3 ∆P < 14 cmH2O), high ∆P group (Day 1 ∆P ≥ 14 cmH2O and Day 3 ∆P ≥ 14 cmH2O), and increment group (Day 1 ∆P < 14 cmH2O and Day 3 ∆P ≥ 14 cmH2O). The 60-day survival significantly differed among the four groups (log-rank test, p = 0.0271). Compared with the low ΔP group, patients in the decrement group did not have lower 60-day survival (adjusted hazard ratio 0.72; 95% confidence interval [CI] 0.31-1.68; p = 0.4448), while patients in the increment group had significantly lower 60-day survival (adjusted hazard ratio 1.96; 95% CI 1.11-3.44; p = 0.0198). CONCLUSIONS: Daily ∆P remains an important predicting factor for survival in patients with ARDS. Serial changes in daily ΔP might be more informative than a single Day 1 ΔP value in predicting survival of patients with ARDS.

Photoplethysmography-derived approximate entropy and sample entropy as measures of analgesia depth during propofol-remifentanil anesthesia.

The ability to monitor the physiological effect of the analgesic agent is of interest in clinical practice. Nonstationary changes would appear in photoplethysmography (PPG) during the analgesics-driven transition to analgesia. The present work studied the properties of nonlinear methods including approximate entropy (ApEn) and sample entropy (SampEn) derived from PPG responding to a nociceptive stimulus under various opioid concentrations. Forty patients with ASA I or II were randomized to receive one of the four possible remifentanil effect-compartment target concentrations (Ceremi) of 0, 1, 3, and 5 ng·ml-1 and a propofol effect-compartment target-controlled infusion to maintain the state entropy (SE) at 50 ± 10. Laryngeal mask airway (LMA) insertion was applied as a standard noxious stimulation. To optimize the performance of ApEn and SampEn, different coefficients were carefully evaluated. The monotonicity of ApEn and SampEn changing from low Ceremi to high Ceremi was assessed with prediction probabilities (PK). The result showed that low Ceremi (0 and 1 ng·ml-1) could be differentiated from high Ceremi (3 and 5 ng·ml-1) by ApEn and SampEn. Depending on the coefficient employed in algorithm: ApEn with k = 0.15 yielded the largest PK value (0.875) whereas SampEn gained its largest PK of 0.867 with k = 0.2. Thus, PPG-based ApEn and SampEn with appropriate k values have the potential to offer good quantification of analgesia depth under general anesthesia.

[Emotion Recognition Based on Multiple Physiological Signals].

Emotion is a series of reactions triggered by a specific object or situation that affects a person's physiological state and can, therefore, be identified by physiological signals. This paper proposes an emotion recognition model. Extracted the features of physiological signals such as photoplethysmography, galvanic skin response, respiration amplitude, and skin temperature. The SVM-RFE-CBR(Recursive Feature Elimination-Correlation Bias Reduction-Support Vector Machine) algorithm was performed to select features and support vector machines for classification. Finally, the model was implemented on the DEAP dataset for an emotion recognition experiment. In the rating scale of valence, arousal, and dominance, the accuracy rates of 73.5%, 81.3%, and 76.1% were obtained respectively. The result shows that emotional recognition can be effectively performed by combining a variety of physiological signals.

Lacticaseibacillus paracasei PS23 increases ghrelin levels and modulates microbiota composition: a post-hoc analysis of a randomized controlled study.

Muscle damage can occur due to excessive, high-intensity, or inappropriate exercise. It is crucial for athletes and sports enthusiasts to have access to ways that expedite their recovery and alleviate discomfort. Our previous clinical trial demonstrated the anti-inflammatory and muscle damage-ameliorating properties of Lacticaseibacillus paracasei PS23 (PS23), prompting us to further explore the role of this probiotic in muscle damage recovery. This post-hoc analysis of a randomized controlled study investigated potential mediators between the intake of PS23 and the prevention of strength loss after muscle damage. We recruited 105 students from a sports university who had participated in the previously published clinical trial. These participants were randomly allocated to three groups, receiving capsuled live PS23 (L-PS23), heat-treated PS23 (HT-PS23), or a placebo over a period of six weeks. Baseline and endpoint measurements were taken for the levels of circulating ghrelin and other blood markers, stress, mood, quality of life, and the fecal microbiota. A significant increase in ghrelin levels was recorded in the L-PS23 group compared to the other groups. Additionally, both L-PS23 and HT-PS23 interventions led to positive shifts in the gut microbiota composition, particularly in elevated Lacticaseibacillus, Blautia, and Lactobacillus populations. The abundance of these bacteria was positively correlated with exercise performance and inversely correlated with inflammatory markers. In conclusion, dietary supplementation with PS23 may enhance exercise performance and influence muscle damage by increasing ghrelin levels and modulating the gut microbiota composition. Further clarification of the possible mechanisms and clinical implications is required.

Effects of chronic fluorosis on the expression of VEGF/PI3K/AKT/eNOS in the gingival tissue of rats with orthodontic tooth movement.

It has been reported that the force of orthodontic correction triggers periodontal tissue remodeling by affecting angiogenesis. However, the manifestation of the vascular response to orthodontic tooth movement in the setting of chronic fluorosis is unclear. The aim of the present study was to preliminarily explore the effect of orthodontic treatment on the angiogenesis of gingival tissue in rats with chronic fluorosis by monitoring changes in the expression of vascular endothelial growth factor (VEGF), phosphatidylinositol-3 kinase (PI3K), AKT (or protein kinase B) and endothelial nitric oxide synthase (eNOS) in the gingival tissue. A total of 60 rats were randomly divided equally into the orthodontic group (O group; n=30) and fluorosis orthodontic group (FO group; n=30). Each of these groups was divided into 0-, 3-, 7-, 14- and 21-day groups (n=6/group). Fluorosis and orthodontic tooth movement models were established, and rats in each group were sacrificed for tissue sampling at the corresponding time points. Tissue morphology was observed via hematoxylin and eosin (H&E) staining. The protein and mRNA expression levels of VEGF, PI3K, AKT and eNOS in gingival tissue were detected by western blotting and reverse transcription-quantitative polymerase chain reaction, respectively. The H&E staining images showed that the FO group had smaller blood vessels and reduced vascular proliferation compared with the O group. Furthermore, the mRNA and protein expression levels of VEGF, PI3K, AKT and eNOS were reduced in the gingiva of rats in the FO group compared with the O group, and certain reductions were significant during the delayed tooth movement period. In addition, with the extension of the application of orthodontic stress, the mRNA and protein expression levels of VEGF, PI3K, AKT and eNOS in the gingiva of the O and FO groups showed a trend of increasing at first and subsequently decreasing, which corresponds with the tooth movement cycle. In conclusion, chronic fluorosis may inhibit the angiogenesis and the expression of the VEGF/PI3K/AKT/eNOS pathway in gingival tissue of orthodontic tooth movement.

Gestational diabetes and risk of perinatal depression in low- and middle-income countries: a meta-analysis.

Background: The relationship between gestational diabetes (GDM) and the risk of depression has been thoroughly investigated in high-income countries on their financial basis, while it is largely unexplored in low- and middle- income countries. This meta-analysis aims to assess how GDM influences the risk of perinatal depression by searching multiple electronic databases for studies measuring the odds ratios between them in low- and middle-income countries. Methods: Two independent reviewers searched multiple electronic databases for studies that investigated GDM and perinatal mental disorders on August 31, 2023. Pooled odds ratios (ORs) and confidence intervals (CIs) were calculated using the random effect model. Subgroup analyses were further conducted based on the type of study design and country income level. Results: In total, 16 observational studies met the inclusion criteria. Only the number of studies on depression (n=10) satisfied the conditions to conduct a meta-analysis, showing the relationship between mental illness and GDM has been overlooked in low- and middle-income countries. Evidence shows an elevated risk of perinatal depression in women with GDM (pooled OR 1.92; 95% CI 1.24, 2.97; 10 studies). The increased risk of perinatal depression in patients with GDM was not significantly different between cross-sectional and prospective design. Country income level is a significant factor that adversely influences the risk of perinatal depression in GDM patients. Conclusion: Our findings suggested that women with GDM are vulnerable to perinatal depressive symptoms, and a deeper understanding of potential risk factors and mechanisms may help inform strategies aimed at prevention of exposure to these complications during pregnancy.

Vegetation response to large-scale mountain excavation and city construction projects on the Loess Plateau of China.

Since 2012, the "Mountain Excavation and City Construction" (MECC) project has been implemented extensively on the Loess Plateau of China, transforming gullies into flat land for urban sprawl by leveling loess hilltops to fill in valleys. However, this unprecedented human activity has caused widespread controversy over its unknown potential ecological impacts. Quantitative assessment of the impacts of the MECC project on the vegetation is key to ecological management and restoration. Taking the largest MECC project area on the Loess Plateau, Yan'an New District (YND), as the study area, this study investigated the spatiotemporal pattern of vegetation dynamics before and after the implementation of the MECC project using a multitemporal normalized difference vegetation index (NDVI) time series from 2009 to 2023 and explored the response of vegetation dynamics to the large-scale MECC project. The results showed that the vegetation dynamics in the YND exhibited significant spatial and temporal heterogeneity due to the MECC project, with the vegetation in the project-affected areas showing rapid damage followed by slow recovery. Vegetation damage occurred only in the project-affected area, and 84 % of these areas began recovery within 10 years, indicating the limited impact of the large-scale MECC project on the regional vegetation. The strong correlation between vegetation dynamics and the MECC project suggested that the destruction and recovery of vegetation in the project-affected areas was mainly under anthropogenic control, which highlights the importance of targeted ecological policies. Specifically, the MECC project induced local anthropogenic damage to the plant population structure during the land creation period, but regeneration and rational allocation of the vegetation were achieved through urbanization, gradually forming a new balanced ecological environment. These findings will contribute to a full understanding of the response of vegetation to such large-scale engineering activities and help local governments adopt projects or policies that facilitate vegetation recovery.

Mechanism of Lian Hua Qing Wen capsules regulates the inflammatory response caused by M1 macrophage based on cellular experiments and computer simulations.

PURPOSE: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. METHODS: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. RESULTS: Macrophages had 140,690 gene targets, inflammatory response had 12,192 gene targets, intersection gene targets were 11,772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. CONCLUSION: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.

Heart rate variability in children and adolescents with major depressive disorder: A systematic review and meta-analysis.

Although reduced heart rate variability (HRV) has been observed in adults with major depressive disorder (MDD), the correlation between HRV and MDD in children and adolescents remains uncertain and requires to be systematically reviewed. Our meta-analysis included ten articles comprising 410 MDD patients and 409 healthy controls. Adolescents with MDD showed significant reductions in most HRV measures, such as HF-HRV, RMSSD, and PNN50, and depressive symptom severity was statistically associated with RMSSD, HF-HRV, and LF/HF ratio. A large heterogeneity across studies was detected. Sensitivity analysis revealed that removal of a specific study would significantly decline the heterogeneity for measures of HF-HRV, LF-HRV, and SDNN, and meta-regression analysis found that sample size and year of publication substantially moderated the differences between depressed samples and controls in RMSSD. Compared with adults, depression-induced autonomic dysfunction was more detectable in children and adolescents with substantial effects. Moreover, excluded studies which reported both HRV and MDD or depression symptoms were summarized based on objectives. Findings indicate that it is promising for HRV to be an appropriate and objective candidate biomarker for clinically depressed children and adolescents.

Distinguishing preeclampsia using the falling scaled slope (FSS) --- a novel photoplethysmographic morphological parameter.

BACKGROUND: Preeclampsia (PE) presence could lead to hemodynamic changes. Previous research suggested that morphological parameters based on photoplethysmographic pulse waves (PPGW) could help diagnose PE. AIM: To investigate the performance of a novel PPGPW-based parameter, falling scaled slope (FSS), in distinguishing PE. To investigate the advantages of the machine learning algorithm over the conventional statistical methods in the analysis. METHODS: Eighty-one pieces of PPGPW data were acquired for the study (PE, n = 44; normotensive, n = 37). The FSS values were calculated and used to construct a PE classifier using the K-nearest neighbors (KNN) algorithm. A predicted PE state varying from 0 to 1 was also calculated. The classifier's performance in distinguishing PE was evaluated using the ROC and AUC. A comparison was conducted with previously published PPGPW-based models. RESULT: Compared to the previous PPGPW-based parameters, FSS showed a better performance in distinguishing PE with an AUC value of 0.924, the best threshold of 0.498 could predict PE with a sensitivity of 84.1% and a specificity of 89.2%. As for the analysis method, training a classifier using the KNN algorithm had an advantage over the conventional statistical methods with the AUC values of 0.878 and 0.749, respectively. CONCLUSION: The result indicated that FSS might be an effective tool for identifying PE. Moreover, the machine learning algorithm could further help the data analysis and improve performance. [Figure: see text].

Physiological feedback technology for real-time emotion regulation: a systematic review.

Background: Previous studies suggest that physiological feedback can be an effective method for emotion regulation (ER). However, studies on the specific effects of physiological feedback have shown conflicting results due to inconsistencies in study designs. Therefore, we present this systematic review to further validate the effectiveness of physiological feedback for ER, clarify its specific effects, as well as summarize the factors that influence its effectiveness. Method: This systematic review following PRISMA guidelines covers all studies using physiological feedback in emotions. A literature search was conducted in Web of Science, PubMed, PsychINFO, China National Knowledge Infrastructure, and WANFANG DATA. And a standardized quality assessment was performed. Results: We identified 27 relevant articles (25 studies), and the majority of these studies showed a significant regulatory effect of physiological feedback on different emotions. The feedback's content, explanation, authenticity, real-time capability, and modality were the key factors that influenced its effects, and this technology will achieve its optimal ER effect when these factors are considered comprehensively. Conclusions: These findings further confirmed the effectiveness of physiological feedback as an ER method, as well as providing key factors that should be addressed in its application. Meanwhile, due to the limitations of these studies, more well-designed studies are still needed.

On the Trail of Molecular Hydrophilicity and Hydrophobicity at Aqueous Interfaces.

Uncovering microscopic hydrophilicity and hydrophobicity at heterogeneous aqueous interfaces is essential as it dictates physico/chemical properties such as wetting, the electrical double layer, and reactivity. Several molecular and spectroscopic descriptors were proposed, but a major limitation is the lack of connections between them. Here, we combine density functional theory-based MD simulations (DFT-MD) and SFG spectroscopy to explore how interfacial water responds in contact with self-assembled monolayers (SAM) of tunable hydrophilicity. We introduce a microscopic metric to track the transition from hydrophobic to hydrophilic interfaces. This metric combines the H/V descriptor, a structural descriptor based on the preferential orientation within the water network in the topmost binding interfacial layer (BIL) and spectroscopic fingerprints of H-bonded and dangling OH groups of water carried by BIL-resolved SFG spectra. This metric builds a bridge between molecular descriptors of hydrophilicity/hydrophobicity and spectroscopically measured quantities and provides a recipe to quantitatively or qualitatively interpret experimental SFG signals.

Unique profile on the progress free survival and overall survival in patients with advanced non-small cell lung cancer in the Qujing area, Southwest China.

Background: China's southwestern region, Qujing, harbors a high incidence of non-small cell lung cancer (NSCLC) and related mortality. This study was designed to reveal the impact of an immune-related prognostic signature (IRPS) on advanced NSCLC in the Qujing. Methods: Tissue specimens from an independent cohort of 37 patients with advanced NSCLC were retrospectively evaluated to determine the relationship between the IRPS estimated by next-generation sequencing (NGS) and clinical outcome. To compare the IRPS in tissue and the clinical outcomes between Qujing and non-Qujing populations, we analyzed datasets of 23 patients with advanced NSCLC from The Cancer Genome Atlas (TCGA) database. In addition, an independent cohort (n=111) of blood specimens was retrospectively analyzed to determine the relationship between the IRPS and clinical outcome. Finally, we evaluated the utility of the blood IRPS in classifying 24 patients with advanced NSCLC who might benefit from immunotherapy. Results: In cohort 1, the Qujing population with tTMB-H (≥ 10 mutations/Mb) or KRAS mutations had shorter progression-free survival (PFS) (hazard ratio [HR] 0.37, 0.14 to 0.97, P = 0.04; HR 0.23, 0.08 to 0.66, P < 0.01) and overall survival (OS) (HR 0.05, 0.01 to 0.35, P < 0.01; HR 0.22, 0.07 to 0.66, P < 0.01). In cohort 2 of the Qujing population, bTMB-H (≥ 6 mutations per Mb) and KRAS mutations were related to PFS (HR 0.59, 0.36 to 0.99, P = 0.04; HR 0.50, 0.26 to 0.98, P = 0.04) and OS (HR 0.58, 0.35 to 0.96, P = 0.03; HR 0.48, 0.25 to 0.93, P = 0.03). Notably, the Qujing population with bTMB-H had superior PFS (HR 0.32, 0.09 to 1.09, P = 0.01), OS (HR 0.33, 0.10 to 1.13, P < 0.01) and objective response rates (ORRs) (83.3% vs. 14.3% vs. 20.0%, P <0.01) to immunotherapy than other populations. Conclusions: These findings show that tTMB, bTMB and KRAS mutations appear to be independent validated IRPSs that predict the clinical outcomes of Qujing populations with advanced NSCLC and that bTMB may be used as a reliable IRPS to predict the clinical benefit from anti-PD-1 therapies among populations from Qujing with advanced NSCLC.

Therapeutic effect of captopril combined with phosphocreatine sodium on viral myocarditis.

OBJECTIVE: To analyze the therapeutic effect of captopril combined with phosphocreatine sodium in patients with viral myocarditis. METHODS: A total of 140 patients with infectious myocarditis who received treatment in Hanzhong City People's Hospital from December 2019 to January 2022 were retrospectively enrolled as study subjects. 61 of them were treated with captopril and constituted the control group (CG), and the remaining 79 who received phosphocreatine sodium in addition to captopril were the research group (RG). Variables were observed and compared between the two groups, including clinical efficacy, adverse reactions during treatment, and changes in myocardial enzymes, cardiac function, troponin, and inflammatory factors. According to therapeutic effect, those patients with marked results were categorized as the significant improvement group, and those whose results were just effective or ineffective were the insignificant improvement group. The risk factors affecting the efficacy of the patients were analyzed by logistic regression. RESULTS: Compared to the CG, the RG had greater decreases in aspartate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), creatine kinase (CK), and lactate dehydrogenase (LDH) (all P < 0.05). The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (FS), and left ventricular stroke volume (SV) in the RG increased significantly more after treatment (P < 0.05), while the levels of high-sensitivity troponin I (cTnI) and cardiac troponin T (cTnT) decreased more significantly (P < 0.05) compared to the CG. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the RG were more down-regulated (P < 0.05), and they had a higher overall response rate after treatment (P < 0.05). However, there was no significant difference in the incidence of adverse reactions between these two groups (P > 0.05). Multivariate logistic regression analysis showed that CK-MB, LVEF, cTnI, and cTnT were independent factors affecting the efficacy. CONCLUSION: Captopril combined with phosphocreatine sodium can reduce the inflammatory response in patients with infectious myocarditis, improve cardiac function, and improve the therapeutic efficacy.

A General Education Course in Medical Devices Innovation at Zhejiang University.

Innovation and development in medical devices are of great significance for overcoming the problems such as the increasing costs of healthcare and the widening societal inequity in medical technologies. This paper presents the design and outcomes of a general education course in medical devices innovation offered for an eight-week quarter each year since Spring 2018 at Zhejiang University. The course consists of two modules, lectures and team project, both of which are well designed based on the entire innovation process spanning needs finding, concept generation, prototyping, and strategy development. A professional teaching team with eight experts from various disciplines and institutes has been established as well. Since its inception, 296 students from 34 majors have participated and 71 original projects have been proposed. The results of self-assessment questionnaires showed that the course had equipped students with broader fundamentals and specialized knowledge, and stronger skills in innovation and teamwork, which provide a solid foundation for students' future innovation practice.